P1572: COVID-19 MORTALITY IN HIGH-RISK PATIENTS AFTER ALLO-HSCT AND CAR-T: IMPROVED OUTCOME THROUGH A PANDEMIC.
Authors: Daniele Sannipoli, Gariazzo Camilla, Francesca Farina, Elisa Diral, Alessandro Bruno, Daniela Clerici, Sarah Marktel, Luca Canziani, Gloria Catalano, Paolo Fiore, Chiara Oltolini, Patrizia Rovere Querini, Consuelo Corti, Fabio Ciceri, Giordano Vitali, Maria Teresa Lupo-Stanghellini
Journal: HemaSphere (2023)

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Patients with haematologic malignancies treated with allogeneic stem cell transplantation (HSCT) or chimeric antigen receptor T (CAR-T) cell therapy who experienced SARS-CoV-2 infection during the omicron wave showed to have considerably higher mortality rates compared to immunocompetent patients with omicron infection. Nevertheless, case fatality rates among high-risk COVID-19 patients decreased throughout the pandemics in conjunction with the improvement of prevention policies as well as the rise of more efficient treatments. Aims: Our aim is to highlight how the optimization of a combined system of prophylactic and therapeutic strategies impacts the outcome of omicron infection in a group of patients with high-risk for severe COVID-19. Methods: We prospectively analysed clinical data from a cohort of patients (n=81) who underwent cell therapy and were infected with omicron variant of SARS-CoV-2 between January and November 2022, for a total of 88 cases. All patients were referred to a COVID-19 dedicated outpatient clinic or to general practitioners and were closely monitored within a standardized post-transplant follow-up. Results: We observed 88 SARS-CoV-2 infections in 81 patients, of which 68 experienced mild or moderate symptoms, while thirteen were complicated with interstitial pneumonia, which in six cases required hospitalisation. Median duration of symptoms was 5-7 days while the median time of positivity was 3-4 weeks. Notably, we recorded 9 cases of long-term positivity (>4 weeks), among which 2 cases overcame 12 weeks of positive tests. Remarkably, 7/9 of these patients had a history of chronic GvHD and 1/9 had persistent B cell aplasia after CAR-T cell therapy. We recommended mRNA SARS-CoV-2 vaccination to all patients from the third month after HSCT and from the sixth month after CAR-T cell therapy, according to ECIL-7 and ECIL-9 guidelines: in our cohort, 57 patients had received at least 1 dose of vaccine after cell therapy, while in 24 patients no dose of vaccine was administered after HSCT; among them, 19 patients were not eligible for vaccination, while 5 patients refused vaccination. Furthermore, starting from April 2022, prophylaxis was improved with the administration of Tixagevimab-Cilgavimab to all patients treated with HSCT or CAR-T cell therapy. All patients were classified at high risk for severe COVID-19 according to AIFA (Italian Medicines Agency) indications, thus being eligible to antiviral drugs: 19 patients received Nirmatrelvir/Ritonavir, while a course of Remdesivir was administered to 21 patients. Fourteen patients received infusion of monoclonal antibodies: 12 received Sotrovimab, one patient received Casivirimab/Imdevimab and one Bamlanivimab/Etesevimab. Eventually, 22 patients did not receive any specific treatment. Thirteen patients received a combined treatment. Overall, 4 patients (4.9%) died while positive for SARS-CoV-2: among them, three died for disease progression, while one died for infective complication and concomitant GvHD and poor graft function. Summary/Conclusion: Our experience during the omicron wave confirms the decrease of case fatality rate among a cohort of patients who are intrinsically at higher risk of infection-related mortality. In this setting, we underline the paramount role played by a combination strategy based on both prevention, through prophylactic measures such as individual-level prevention steps, vaccines and monoclonal antibodies, as well as a dedicated hospital organization, and treatment as a key to further implement the outcomes of COVID-19 (figure 1).Keywords: CAR-T, COVID-19, HSCT